Maternal care of offspring requires rapid neurobehavioral changes, including plasticity within circuits specialized for processing infant cues such as crying. Neuroendocrine signals are important for neuroplasticity, including release of the peptide hormone oxytocin. Oxytocin is released from the hypothalamus and is important for childbirth and lactation. Oxytocin also acts in the brain where it is believed to increase the salience of social information, enhancing pair bonding and maternal behavior. Clinical studies suggest that oxytocin is a promising therapeutic agent, with patients sometimes engaging more successfully in social interactions. There is a high rate of child maltreatment and neglect, but training programs and interventions that teach parents to detect and respond to social signals have had some success. These therapies would benefit from understanding the interactions between infant social cues, oxytocin modulation, and neuroplasticity relevant for maternal behaviors. In this proposal, we will study the neural circuitry, plasticity, and behavioral effects of oxytocin in the context of maternal behavior in mice. We study neurobehavioral responses to infant ultrasonic vocalizations by maternal caregivers, which requires experience with pups and is facilitated by oxytocin. We will study the sequence of auditory-based maternal behaviors first expressed by pup-nave females co-housed with mothers and pups. The central hypothesis is that social contact with dam or pups releases oxytocin, interacting with pup calls to induce plasticity in auditory cortex. We will use in vivo recording and imaging, combined with behavior and optogenetics to examine how cortex is modified by oxytocin and pup call sounds, building on our past work on cortical plasticity and modulation. In Aim 1 we measure activity in auditory cortex during co-housing, relating retrieval behavior to cortical plasticity. In Aim 2, we examine the how oxytocin modulates excitatory and inhibitory cells and synapses for processing auditory social signals. Finally in Aim 3 we ask how oxytocin is appropriately released by infant cues, to initiate these auditory cortical changes and shape maternal behavior in newly- maternal mice. In summary, here we will use behavioral experiments combined with optogenetics and in vivo recordings to ask how oxytocin is released and affects auditory cortex, to enable maternal recognition of infant distress calls. These experiments will provide fundamental and urgently-needed data on the neural circuitry and functional consequences of oxytocin signaling in the mammalian brain, in the context of a deep and long-standing question in neuroscience: how are specific neural circuits specialized for sensory processing and maternal behavior?